The Program Project will unite established investigators in an intensive program of research exploring the interrelationships of thyroid axis hormones, brain and behavior, with the specific goal of better understanding the role played by this interaction in the genesis, expression and treatment of affective illness, particularly bipolar disorder. Four interrelated projects are proposed exploring various aspects of thyroid physiology and genetics in normal human beings, those with manic depressive illness, and rapid cycling bipolar disorder; in animals, the possible physiological and pharmacological underpinnings of the association are investigated through circadian models, photoperiod challenge, and the study of those psychotropic agents usually employed in the management of bipolar disease: Project I (P.C. Whybrow, MD, PI) - Thyroid Hormones and Affective Illness: Clinical Studies Project II (R.C. Gur, PhD, PI) - Thyroid Function, Affective Disturbance and Regional Cerebral Blood Flow Project III (R.A. Price, PhD, PI) - Genetic Family Study of Thyroid Function in Rapid Cycling Disease Project IV (M.B. Dratman, MD, PI) - Psychopharmacology and Thyroid Hormone Processing in Brain These individual projects are coordinated and supported by two integrating cores that assure standard procedures: Core 1 (M.S. Kreider, PhD, PI) - Radioimmunoassay and Chemical Analyses Core 2 (L. Muenz, PhD, PI) - Data Management and Statistics